Hemodialysis is currently required by more than 200,000 Americans with this number expected to climb significantly in the next decade. During each dialysis session, only a portion of the waste products normally eliminated by the kidneys is actually removed. The subject device of this research proposal is designed to be more efficient than current dialyzer units and at the same time present smaller foreign surface area to minimize deleterious blood-biomaterial interactions. The long-term object of this research is to complete the development of a highly efficient hemodialyzer, Renal Flow. This device achieves its high efficiency through the use of active mixing whereby the dialyzer element is rotated within the blood environment to minimize fluid phase resistance resulting in increased mass transfer efficiency. This rotational motion also imparts energy to the blood which could obviate the need for a separate blood pump as currently required by dialysis machines. Increased efficiency and elimination of unnecessary components should allow for more complete removal of waste products while minimizing the amount of blood contacting surface area. In Phase II, we propose to increase our fabrication efficiency and yield by injection molding components, developing new methods of fiber array production, utilizing clean room production, and automating device fabrication. In addition, we propose to integrate the RenalFlow controller into a clinically available dialysis console. Multiple prototypes using various fiber types, fiber densities, and surface areas will be constructed in Year 1 and evaluated. The most promising design will then be optimized and fully characterized in Year 02. Comprehensive in vitro and ex vivo evaluations are an integral part of this program. We propose to use bovine blood in vitro for mass transfer calculations and calves with chronic hemodialysis shunts for multiple RenalFlow biocompatibility evaluations. Dialyzer cartridges will be reprocessed per current clinical practice to mimic actual use.